The need for an adjuvant in the administration of immunological substances has long been recognized and considerable work has been done to discover substances which when added to an antigen or other immunological substance would potentiate its antigenic activity and thereby its antibody stimulating capacity. To date, many such adjuvants have been discovered such as the use of alum precipitation of antigens, combining certain specific antigens some of which would potentiate the activity of the others in the mixture, the use of calcium phosphate particularly to potentiate influenza antibody production and the similar use of Staphylococcus toxin which appear to improve the antibody response to certain antigens. Several other adjuvant substances also have been considered such as tapioca, calcium or magnesium salts, tannin and the like which when added to certain specific antigens would increase the antibody titer over that obtainable when the antigen alone was administered.
Immunological adjuvants are used to increase the amount of antibody produced and to reduce the quantity of antigen and the frequency of injection. Aluminum adjuvants are widely used, and although considered safe in man, sterile abscesses and persistent nodules may follow their use. Complete Freund's adjuvant, an oil-in-water emulsion containing tubercle bacilli, is more potent than the aluminum adjuvants. However, the deleterious side effects, including severe granuloma formation, allergic responses, and oil retention in the tissues, preclude its use in man.
The present invention represents the development of a potent, well-tolerated adjuvant for incorporation in a range of vaccines and antigen compositions for use in man and animals. The antigen itself may be in the form of purified or partially purified antigen derived from bacteria, viruses, or rickettsia, or the antigen may be an allergen such as pollens, dusts, danders, or extracts of the same or the antigen may be in the form of a poison or a venom derived from poisonous insects or reptiles. In all cases the antigen will be in the form which when introduced into a suitable host will either induce active immunity by the production therein of antibodies against the specific antigen or, in the case of an allergen, will aid in alleviating the symptoms of the allergy due to the specific allergen. The antigens can be used either singly or in combination. Antigens of particular importance are derived from bacteria such as H. pertussis, Leptospira pomona and icterohaemorrhagiae, S. typhosa, S. paratyphi A and B, C. diphtheriae, C. tetani, C. botulinum, C. perfringens, C. feseri and other gas gangrene bacteria, B. anthracis, P. pestis, P. multocida, V. cholerae and the like; from viruses as poliovirus (multiple types), adeno virus (multiple types), parainfluenza virus (multiple types), measles, mumps, respiratory syncytial virus, influenza (multiple types), shipping fever virus (SF4), Western and Eastern equine encephalomyelitis, Japanese B. encephalomyelitis, Russian Spring Summer encephalomyelitis, hog cholera virus, fowl pox, Newcastle disease virus, rabies, feline and canine distemper and the like viruses, from rickettsiae as epidemic and endemic typhus or other members of the spotted fever group, from various spider and snake venoms or any of the known allergens such as ragweed, house dust, pollen extracts, grass pollens and the like.
A number of substances, some of which are also inducers of interferon, have been reported to have adjuvant properties. These are listed in "Immunological Adjuvants," World Health Organization Technical Report Series No. 595. In addition to this list is the reported adjuvant activity of aliphatic nitrogeneous bases by D. Gall, Immunology, 11, 369 (1966) and lysolecithin analogues by O. Shannegard and G. Roupe, Int. Arch. Allergy Appln. Immun., 51, 198 (1976).